Aliases: DOA1, NDMSBA, PLA2P, PLAP
Chromosome No: 9
Chromosome Band: 9p21.2
Genetic Category: Functional-Syndromic-Rare single gene variant-Rare single gene variant/Functional
ASD Reports: 8
Recent Reports: 0
Annotated variants: 5
Associated CNVs: 9
Evidence score: 2
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Relevance to Autism
A de novo missense variant in the PLAA gene (p.Ile609Thr) was identified in a male ASD proband from a simplex family from the MSSNG cohort in Yuen et al., 2007; functional assessment of this variant and a previously unreported ASD-associated missense variant in the PLAA gene (p.Leu795Met) in Iacomino et al., 2024 demonstrated that both missense variants affected the PLAA interactome and resulted in significantly reduced binding to VCP/p97. A de novo splice-region variant in this gene was also identified in an ASD proband from the Simons Simplex Collection (Zhou et al., 2022).
Molecular Function
Predicted to enable ubiquitin binding activity. Involved in cellular response to lipopolysaccharide; macroautophagy; and positive regulation of phospholipase A2 activity. Located in cytoplasm; extracellular exosome; and nucleus. Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (Papadopoulos et al., 2017). Biallelic variants in the PLAA gene are responsible for neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA; OMIM 617527), an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profoundly impaired intellectual development and severely impaired or absent motor function (Falik Zaccai et al., 2017; Hall et al., 2017).
External Links
